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By I. Tippler. Loyola University, Chicago. 2018.

What is the prob- ability that the variations of measurements are due to statistical varia- tions of the quantity? The majority of radionuclides are arti- ficially produced in the cyclotron and reactor generic lady era 100 mg amex pregnancy zumba dvd. Some short-lived radionu- clides are available from the so-called radionuclide generators in which long-lived parents are loaded and decay to short-lived daughters generic lady era 100 mg without prescription women's health clinic yonkers ny. These accelerated particles can possess a few kiloelectron volts (keV) to several billion electron volts (BeV) of kinetic energy depending on the design of the cyclotron. Because charged particles move along the circular paths under the magnetic field with gradually increasing energy, the larger the radius of the particle trajectory, the higher the kinetic energy of the particle. The charged particles are deflected by a deflector (D) through a window (W) outside the cyclotron to form an external beam. When targets of stable elements are irradiated by placing them in the external beam of the accelerated particles or in the internal beam at a given radius inside a cyclotron, the accelerated particles interact with the target nuclei, and nuclear reactions take place. In a nuclear reaction, the incident particle may leave the nucleus after interaction with a nucleon, leaving some of its energy in it, or it may be completely absorbed by the nucleus, depending on the energy of the incident particle. In either case, a nucleus with excitation energy is formed and the excitation energy is disposed of by the emission of nucleons (i. Particle emission is followed by g-ray emission when the former is no longer energetically feasible. Depending on the energy deposited by the incident particle, several nucleons are emitted randomly from the irradiated target nucleus, 44 Cyclotron-Produced Radionuclides 45 Fig. A and B, dees with vacuum; D, deflector; S, ion source; V, alternating voltage; W, window. As the energy of the irradi- ating particle is increased, more nucleons are emitted, and therefore a much wider variety of nuclides is produced. Medical cyclotrons are compact cyclotrons that are used to produce rou- tinely short-lived radionuclides, particularly those used in positron emission tomography. In these cyclotrons, protons, deuterons, and a-particles of low- to-medium energy are available. These units are available commercially and can be installed in a relatively small space. An example of a typical cyclotron-produced radionuclide is 111In, which is produced by irradiating 111Cd with 12-MeV protons in a cyclotron. The nuclear reaction is written as follows: 111Cd(p, n)111In where 111Cd is the target nuclide, the proton p is the irradiating particle, the neutron n is the emitted particle, and 111In is the product radionuclide. In this case, a second nucleon may not be emitted, because there is not enough energy left after the emission of the first neutron. The excitation energy that is not sufficient to emit any more nucleons will be dissipated by g-ray emission. As can be understood, radionuclides produced with atomic numbers dif- ferent from those of the target isotopes do not contain any stable (“cold,” or “carrier”) isotope detectable by ordinary analytical methods, and such preparations are called carrier-free. In practice, however, it is impossible to have these preparations without the presence of any stable isotopes. The target material for irradiation must be pure and preferably monoiso- topic or at least enriched isotopically to avoid the production of extrane- ous radionuclides. Because various isotopes of different elements may be produced in a target, it is necessary to isolate isotopes of a single element; this can be accomplished by appropriate chemical methods such as solvent extraction, precipitation, ion exchange, and distillation. Production of Radionuclides + radionuclides are usually neutron deficient and therefore decay by b - emission or electron capture. Reactor-Produced Radionuclides A variety of radionuclides is produced in nuclear reactors. A nuclear reactor 235 is constructed with fuel rods made of fissile materials such as enriched U and 239Pu. Fission is defined as the breakup of a heavy nucleus into two fragments of approximately equal mass, accompanied by the emission of two to three neutrons with mean energies of about 1. In each fission, there is a concomitant energy release of ~200MeV that appears as heat and is usually removed by heat exchangers to produce electricity in the nuclear power plant. Neutrons emitted in each fission can cause further fission of other fis- sionable nuclei in the fuel rod, provided the right conditions exist.

Although cerebrovascular syndromes occur with 10 order 100 mg lady era overnight delivery menstruation questions answers,000 rem (100Sv) purchase 100 mg lady era with amex pregnancy 23 weeks, and result in death, the hemopoietic and gastrointestinal syn- dromes may be managed by bone marrow transplantation and other pro- phylactic treatment. Internal contamination can occur from the inges- tion of contaminated food and water, inhalation of the contaminated air, and diffusion through the skin or wounds. The principle of the treatment of internal contamination primarily involves dilution, displacement by non- radioactive material, complex formation, and blockage. Outer garments such as clothing and shoes can be contaminated by radioactivity from the explosion of a dirty bomb. Such contamination does not constitute a medical emergency and most of it can be removed by taking off these garments. Minor skin contamination can be eliminated by thor- ough washing with water and detergent, and a shower, if appropriate. Skin should not be abraded by a heavy brush, as this may facilitate internal absorption. Radiation Biology the external contamination, the patient must be first managed for the con- dition before decontamination is carried out. Burns and wounds that are not contaminated should be first covered and then decontamination of the other affected areas carried out. If you are outside and close to the explosion of a dirty bomb, cover the nose and mouth with a mask or cloth to reduce the risk of breathing in radioactive dust or smoke. If possible, immediately go inside the building that is not affected by the explosion and remove the outer layer of cloth- ing and shoes and seal them in a plastic bag, if available. If you are inside and close to the incident that has occurred outside, close all the doors and windows and do not leave the building. Local or federal authorities are likely to monitor the food and water in the area of explosion and inform the public of their suitability for consumption. Verification Card for Radioactive Patients After the September 11, 2001 attack on the World Trade Center in New York, numerous security measures have been adopted by the U. Congress has passed laws to establish the Department of Homeland Security to implement and monitor different aspects of these security measures. Security checks of airline passengers, background scrutiny of many visitors and suspected terrorist groups, and implementa- tion of the Patriot Act are some of the examples of these security actions Radiation Phobia 263 that are currently in place. In view of the concerns over the use of dirty bombs by miscreants, the Homeland Security has established checkpoints at various strategic locations such as airports, tunnels, mass transit, bridges, border crossing points, historical monuments, landmarks, and the like, to monitor the transport of dirty bombs containing radioactivity by using radi- ation detectors. One pitfall of this measure is that patients who received radioactive materials for diagnostic and therapeutic purposes may trigger the monitors while passing through these checkpoints and undergo undue hassle with authorities to provide proof that the radioactivity was really from medical uses. Many hospitals are adopting this policy and instruct the patients to carry the card for the period discussed below. A question arises as to how long the patient who has undergone nuclear studies should carry the card. It depends on the half-life of the radionuclide, types of radiations the radionuclide emits, and the biological elimination of the radiotracer from the body. Zuckier (2004) in a paper presented at The Radiological Society of North America annual meeting in Chicago sug- gested the following periods for different radionuclides for the patients to carry the card. One important factor is the graphic images of the devastating effects of the atomic bombs detonated in Hiroshima and Nagasaki in 1945, and to a lesser extent, the images of the Chernobyl reactor accident in 1986. The most noticeable effects of these incidents are death of living species and destruction of property at the site of the explosion and its immediate vicin- ity. Because of these images, many people associate radiation exposure with adverse health effects and death. These images are firmly embedded in the minds of the public causing perpetual fear of radiation. Another flashpoint in creating radiation phobia in the public’s mind is the knowledge of assumption that any level of ionizing radiation is dan- 264 15. Psychological warfare with anecdotal rhetoric among the rival countries possessing nuclear weapons also creates fear of radiation among the public. Dreading effects of radiation on children and future offspring, and long-term damage to property are major concerns of the public. Furthermore, the media often play a role in exacerbating the problem of exposure from radiation accidents. Def- initely, nuclear detonation causes an instantaneous devastating effect on the population and property, and so can be reason for fear and panic.

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Some projects are examining metabonomic patterns in series of patients with metabolic syndromes and comparing them with normal peo- ple buy cheap lady era 100 mg line menopause pajamas. Other studies are examining how a person’s unique metabonomic profile can be used as a guide to personalize diet and exercise regimens for obesity 100 mg lady era sale women's health center vienna va. It is now possible to measure hundreds or thousands of metabolites in small samples of biological fluids or tissues. This enables assessment of the metabolic component of nutritional phenotypes and will enable individualized dietary recom- mendations. The relation between diet and metabolomic profiles as well as between those profiles and health and disease needs to be established. Appropriate technolo- gies should be developed and that metabolic databases are constructed with the right inputs and organization. Moreover, social implications of these advances and plan for their appropriate utilization should be considered. Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Universal Free E-Book Store References 177 Gieger C, Geistlinger L, Altmaier E, et al. Genetics meets metabolomics: a genome-wide associa- tion study of metabolite profiles in human serum. Universal Free E-Book Store Chapter 8 Non-genomic Factors in the Development of Personalized Medicine Introduction Besides genomics other omics, epigenomic and non-genomic factors and biotechnologies have contributed to the development of personalized medicine. Although personalized medicine is considered to be mostly based on pharma- cogenomics, a number of other factors that vary among individuals and should be considered are: • Identification of subpopulation of patients best suited for an existing drug • New drug design for a specific sub-population of patients • Use of an individual patient’s cells or tissues for biological therapies • Cytomics: analysis of disease at single cell level. Among biotechnologies, nanobiotechnology has made important contributions to the development of personalized medicine. They are attributed to circadian rhythms, which are endogenous self-sustained oscillations with a period of ~24 h. These rhythms persist under constant environmental conditions, demonstrating their endogenous nature. Several clock genes and clock-controlled tran- scription factors regulate, at least in part, gene expression in central and/or periph- eral clocks. The rhythms of disease and pharmacology can be taken into account to modulate treatment over the 24-h period, i. The term “chronopharmacology” is applied to variations in the effect of drugs according to the time of their adminis- tration during the day. Most of these genes were previously recognized clock genes that are responsible for the keeping the body’s internal daily rhythm. Universal Free E-Book Store Environmental Factors in Disease 181 The body needs a completely different set of genetic programs to perform activities than it does for sleep and restoration. The knowledge of expression of gene relevant to circadian rhythms might enable identification of drugs whose efficacy and side effects are most likely to be affected by time of administration. The antihypertensive drug Diovan and Ritalin used for attention deficit hyperactivity disorder have half-lives of <6 h, which means that if they are administered at the wrong time, they might break down before having a chance to fully engage with their targets. The timing of drug administration could also explain why some persons in clinical trials seem to respond to a medication while others do not. It should be noted that most studies on mice are performed dur- ing the day, when the animals should be asleep. Humans most often take drugs in the daytime, during their wake cycle, which could explain why drug effects can fail to translate from mice to humans. Already there are several examples of how chronotherapy has improved man- agement of several diseases. A clinical trial of low-dose glucocorticoid chrono- therapy added to disease-modifying treatment produces rapid and relevant improvements in signs and symptoms of rheumatoid arthritis with better results than conventional glucocorticoid administration (Buttgereit et al.

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Two procedures are used for in vitro investigation of the metabolic profile of a drug: incubation with microsomes and incubation with metabolically compe- tent cells lady era 100mg discount women's health center in waco. The major limitation of microsomes is that inhibition parameters may not accu- rately reflect the situation in vivo proven 100mg lady era women's health clinic sf, since the contribution of drug transport is not considered. The best picture of a potential drug-drug interaction can be obtained in metabolically competent hepatocytes. Human hepatocytes in primary culture respond well to enzyme inducers during the first few days; this ability is lost thereafter. Hepatoma cell lines respond poorly to inducers, although the induction of a few isoenzymes has been reported. Primary cultured hepatocytes are still the unique in vitro model that allows global examination of the inductive potential of a drug. Genetically manipulated cell lines that express enzymes and respond to inducers would be more suitable for this purpose as an alternative to the use of human hepatocytes. Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 111 Polymorphism of Drug Transporters Transporters are involved in the transport of proteins, peptides, amino acids, ions and certain drugs. Transport proteins have an important role in regulating the absorption, distribution, and excretion of many medications. Disorders associated with defects in solute transporters, such as severe diarrhea in glucose/galactose malabsorption and pri- mary bile acid malabsorption may be associated with pronounced general changes in drug absorption. Several investigations are aimed at clarifying the role of trans- porters in drug absorption, disposition, and targeting. Another important gene family is the biogenic amine transporters, which regu- late neurotransmitter levels in synaptic transmission, with a number of documented variants that may affect function. These transporters are the direct target receptors for numerous drugs, including antidepressants and cocaine. Allelic variations, in particular of the serotonin transporter, are associated with the modulation of com- plex behavior and may play a significant role in therapy with specific serotonin transporter inhibitors. Variation in neurotransmitter receptors can also be the cause of treatment failure. Genetic polymorphism of the β2-adrenoreceptor can alter the process of signal transduction by these receptors. Polymorphisms in drug target genes that can influence drug response are listed in Table 4. Protein kinases are coded by more than 2,000 genes and thus constitute the largest single enzyme family in the human genome. Amplicon modeling, primer design and assay vali- dation have been established for over 1,600 amplicons within 92 different kinase genes. Kinase mutation mapping can be used to pinpoint responder populations and facilitate the development of person- alized medicine. Effect of Genetic Polymorphisms on Disease Response to Drugs Genetic polymorphism of genes and gene products may influence the disease- modifying effects of drugs. It offers 1,936 high value, biologically relevant markers in 225 drug metabolism enzyme, trans- porter, and transferase genes. Such informa- tion is useful in identifying the responders to drugs and is discussed further in sub- sequent chapters. Ethnic Differences in Drug Metabolism Ethnic differences in drug metabolism are well documented for a number of drugs. The molecular mechanisms responsible for ethnic differences in drug metabolism have been partly clarified because of the advances in molecular biology. Genotype analysis indicates a different frequency for the mutant alleles in different ethnic populations, which results in variations in the frequency of subjects who are homo- zygous for the mutant allele among the extensive metabolizers in different ethnic populations. Ethnic differences in drug metabolism may result from differences in distribution of a polymorphic trait and mutations, which code for enzymes with abnormal activity which occur with altered frequency in different ethnic groups. Ethnic factors, therefore, are an important consideration in individualization of therapy. Gender Differences in Pharmacogenetics There are gender-related differences in pharmacokinetics, which may be related to pharmacogenetic differences in to drug-metabolizing enzymes. Other gender differences in pharmacokinetics may be due to fluctuations in hormone levels in women with menstruation and pregnancy. Moreover, development of diseases such as heart disease and cancer may affect women differently from men.

The percent- 16% 16% ages are the approximate 68% percentages of the scores falling into each portion of the distribution generic lady era 100 mg line women's health center elmhurst hospital. Therefore lady era 100mg low cost women's mental health issues, envision Distribution C: Scores frequently occur that are way above or below 50, so the middle 68% of the distribution is relatively wide and spread out between 38 and 62. X X ■ The standard deviation is interpreted as the average Sample A is ____ (more/less) variable and most amount that scores deviate from the mean. If X 5 10 and S 5 2, then 68% of the scores fall X For the the scores 5, 6, 7, 8, 9, the X 5 7. However, by reworking them, we have less obvious but faster com- putational formulas. Computing the Sample Variance The computational formula for the sample variance is derived from its previous defini- tional formula: we’ve replaced the symbol for the mean with its formula and then re- duced the components. First, X X variability cannot be a negative number because you are measuring the distance scores are from the mean, and the formulas involve squaring each deviation. Then the largest deviation is about 25, so the “average” de- viation will be much less than 25. Strange answers may be correct for strange distributions, but always check whether they seem sensible. A rule of thumb is For any roughly normal distribution, the standard deviation should equal about one-sixth of the range. To find the standard deviation, perform the above 900 166 – steps and then find the square root, so 6 3. The answer depends on whether we add (subtracting is adding a negative number) or multiply (dividing is multiplying by a fraction). Adding a constant to all scores merely shifts the entire distribution to higher or lower scores. We do not alter the relative position of any score, so we do not alter the spread in the data. In the transformed data, the score is now 14, but it is still 2 points away from the new mean of 16. In the same way, each score’s distance from the mean is unchanged, so the standard deviation is unchanged. Multiplying by a constant, however, does alter the relative positions of scores and therefore changes the variability. If we multiply the scores 4, 5, 6, 7, and 8 by 10, they become 40, 50, 60, 70, and 80. The original scores that were 1 and 2 points from the mean of 6 are now 10 and 20 points from the new mean of 60. Each transformed score produces a deviation that is 10 times the original deviation, so the new standard devia- tion is also 10 times greater. The symbol for the known and true population standard deviation is σX (the σ is the lowercase Greek letter s, called sigma). Because the squared standard deviation is the variance, the symbol for the true population variance is σ2. Otherwise the population standard deviation and variance tell us ex- actly the same things about the population that we saw previously for a sample: Both are ways of measuring how much, “on average,” the scores differ from , indicating how much the scores are spread out in the population. And again, 34% of the popula- tion will have scores between and the score that is 11σX above , and another 34% will have scores between and the score that is –1σX below , for a total of 68% falling between these two scores. X X We won’t bother with their computing formulas, because these symbols will appear for you only as a given, when much previous research allows us to know their values. Estimating the Population Variance and Population Standard Deviation We use the variability in a sample to estimate the variability that we would find if we could measure the population. However, we do not use the previous formulas for the sample variance and standard deviation as the basis for this estimate. These statistics (and the symbols S and S2) are used only to describe the variability in a sample. To understand why this is true, say that we measure an entire population of scores and compute its true variance. We then draw many samples from the population and compute the sample variance of each. Sometimes a sample will not perfectly represent the population so that the sample variance will be either smaller or larger than the pop- ulation variance.

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